A model of an intentional self-observing system is proposed based on the structure and functions of astrocyte-synapse interactions in tripartite synapses. Astrocyte-synapse interactions are cyclically organized and operate via feedforward and feedback mechanisms, formally described by proemial counting. Synaptic, extrasynaptic and astrocyte receptors are interpreted as places with the same or different quality of information processing described by the combinatorics of tritograms. It is hypothesized that receptors on the astrocytic membrane may embody intentional programs that select corresponding synaptic and (...) extrasynaptic receptors for the formation of receptor-receptor complexes. Basically, the act of self-observation is generated if the actual environmental information is appropriate to the intended observation processed by receptor-receptor complexes. This mechanism is implemented for a robot brain enabling the robot to experience environmental information as “its own”. It is suggested that this mechanism enables the robot to generate matches and mismatches between intended observations and the observations in the environment, based on the cyclic organization of the mechanism. In exploring an unknown environment the robot may stepwise construct an observation space, stored in memory, commanded and controlled by the intentional self-observing system. Finally, the role of self-observation in machine consciousness is shortly discussed. (shrink)

The self, Joseph LeDoux tells us, is “the totality of the living organism”. Most disciplines in the natural sciences focus on only one or two levels of organization. Indeed, Dmitri Mendeleev figured out the periodic table of the elements without knowing any of the underlying quantum mechanics or stereochemistry. There are, however, at least a dozen levels of organization within the neurosciences — and, if we use a metaphor, we temporarily create yet another. This leads to considerable confusion and arguments (...) at cross purposes over whether learning is an alteration at the level of gene expression, ion channels, synapses, neurons or circuits. Each neuron has thousands of synapses, which produce currents that summate to form an impulse train. But only rarely is the activity of a single neuron sufficient to cause a perception or trigger an action. Neurons usually act as members of ‘committees’ — what Donald Hebb in 1949 called cellassemblies. Just as in academia, one individual may function in different committees on different occasions. A concept, including any explicit memory that we can talk about, is probably formed by such a committee. Implicit memories are less differentiated — they are part of the ‘feltwork’, together with motivations and emotions, that biases the choice of one’s next act. In this well-written 400-page appreciation of behavioural neuroscience, LeDoux argues that synapses are the seat of self. He says, in effect, that you are your memories; that it is the uniqueness of an array of synaptic strengths that distinguishes one twin from another. Fair enough, but why not instead focus on one’s unique array of ion channels? Or neurons, because a neuron is the closest thing we have to a computational unit? Or one’s unique arrangement of those overlapping, redundant hebbian committees? None of these make for a catchy book title, but relating other things to the synapses proves to be a good way of covering a lot of fascinating material at the overlying levels, including a few updates to LeDoux’s earlier book The Emotional Brain. (shrink)

No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels informs the novel hypothesis that: (1) at an inactive synapse, increased mitochondrial ROS production initiates intrinsic apoptosis dependent pruning; and (2) at an active synapse, decreased mitochondrial ROS production masks intrinsic apoptosis dependent (...) pruning. Immature antioxidant defense may enable the developing brain to harness mitochondrial ROS to prune weak synapses. Beyond development, endogenous antioxidant defense constrains mitochondrial (ROS) to mask pruning. Unwanted age‐related synapse loss may arise when mitochondrial ROS aberrantly recapitulate developmental pruning. Placing mitochondrial ROS with their hands on the shears is beneficial in early but deleterious in later life. (shrink)

. Progress in technology has allowed dynamic research on the development of the human brain that has revolutionized concepts. Particularly, the notions of plasticity, neuronal selection, and the effects of afferent stimuli have entered into thinking about brain development. Here I focus on development from the age of four years to early adulthood, during which a 30 percent reduction in some brain synapses occurs that is out of proportion to changes in neuronal numbers. This corresponds temporally with changes in (...) normal child behavior from the loose‐associative, almost schizoid, thinking and art of the four‐year‐old to the more trained, or disciplined, or acculturated—and restrained—personality of the young adult. I propose that the synaptic changes can best be thought of as a winnowing process likely subject to environmental influences. Acquisition of language and the ability to link linguistic cognition to the plastic development of the brain provide a potentially powerful means of explaining the evolutionally explosive development of human cognition and culture. Schizophrenia, a disease that can be envisioned as representing a derangement of synaptic maturation, may provide an entry into the search for genes controlling the processes mediating the unprecedented development of Homo sapiens over the past 40,000 to 70,000 years. The recently completed mapping of the genome of the chimpanzee provides a new frame of reference that may speed the search. (shrink)

Phillips & Silverstein emphasize the gain-control properties of NMDA synapses in cognitive coordination. We endorse their view and suggest that NMDA synapses play a crucial role in biased attentional competition and (visual) working memory. Our simulations show that NMDA synapses can control the storage rate of visual objects. We discuss specific predictions of our model about cognitive effects of NMDA-antagonists and schizophrenia.

The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non-bilaterian metazoans, both with and without neurons and their closest relatives already contain many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non-bilaterian metazoans. The evolution of synapses and neurons are often discussed only from a metazoan perspective leaving (...) a considerable gap in our understanding. By taking an integrative approach we highlight the need to consider different, but extremely relevant phyla and to include the closest unicellular relatives of metazoans, the ichthyosporeans, filastereans and choanoflagellates, to fully understand the evolutionary origin of synapses and neurons. This approach allows for a detailed understanding of when and how the first pre- and postsynaptic signaling machineries evolved. The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Most of our knowledge and recent discussions are biased towards a metazoan perspective, leaving a considerable gap in our understanding. Recent work has now revealed important insights into the emergence and co-regulation of complex synaptic signaling machineries from studies in the closest unicellular relatives of metazoans. (shrink)

We recently described a novel form of stress‐associated bidirectional plasticity at GABA synapses onto hypothalamic parvocellular neuroendocrine cells (PNCs), the apex of the hypothalamus‐pituitary‐adrenal axis. This plasticity may contribute to neuroendocrine adaptation. However, this GABA synapse plasticity likely does not translate into a simple more and less of inhibition because the ionic driving force for Cl−, the primary charge carrier for GABAA receptors, is dynamic. Specifically, stress impairs a Cl− extrusion mechanism in PNCs. This not only renders the steady‐state (...) GABA response less hyperpolarizing but also makes PNCs susceptible to the activity‐dependent accumulation of Cl−. Accordingly, GABA synapse plasticity impacts both the robustness of GABA voltage response and dynamic Cl− loading, imposing nonlinear influences on PNC excitability during circuit activities. This theoretical consideration predicts roles for GABA transmission far more versatile than canonical inhibition. We propose potential impacts of GABA synapse plasticity on the experience‐dependent fine‐tuning of neuroendocrine stress responses. (shrink)

This selective review explores biologically inspired learning as a model for intelligent robot control and sensing technology on the basis of specific examples. Hebbian synaptic learning is discussed as a functionally relevant model for machine learning and intelligence, as explained on the basis of examples from the highly plastic biological neural networks of invertebrates and vertebrates. Its potential for adaptive learning and control without supervision, the generation of functional complexity, and control architectures based on self-organization is brought forward. Learning without (...) prior knowledge based on excitatory and inhibitory neural mechanisms accounts for the process through which survival-relevant or task-relevant representations are either reinforced or suppressed. The basic mechanisms of unsupervised biological learning drive synaptic plasticity and adaptation for behavioral success in living brains with different levels of complexity. The insights collected here point toward the Hebbian model as a choice solution for “intelligent” robotics and sensor systems. Keywords: Hebbian learning; synaptic plasticity; neural networks; self-organization; brain; reinforcement; sensory processing; robot control . (shrink)

A dualistic approach to consciousness is presented that employs Hebbian synaptic dynamics and the basic notion of measurement in science to bridge the so-called explanatory gap between first-person consciousness and third-person science. Unconscious processing by neural circuitry characterizes (i) the neuron as a measuring instrument and (ii) the neural signal as the quantity to be measured. Hebbian synaptic dynamics, effectuating the storage of information, implements the role of an observer of a measurement outcome. The approach extends physical renormalization techniques, as (...) applied to phase changes, to biology. This leads to the proposal of a ramification process in neural systems (brains) from a primitive form of sensation associated with the Hebbian synapse toward more elaborate experiential forms of consciousness (feelings, qualia) associated with hierarchies of neuronal assemblies. Characterizing sensation as a form of mutual information at the synaptic level motivates a relation between consciousness and phase changes of information. (shrink)

A formalism is introduced to represent the connective organization of an evolving neuronal network and the effects of environment on this organization by stabilization or degeneration of labile synapses associated with functioning. Learning, or the acquisition of an associative property, is related to a characteristic variability of the connective organization: the interaction of the environment with the genetic program is printed as a particular pattern of such organization through neuronal functioning. An application of the theory to the development of (...) the neuromuscular junction is proposed and the basic selective aspect of learning emphasized. (shrink)

There are remarkable behavioral, neural, and genetic similarities between the way songbirds learn to sing and human infants learn to speak. Furthermore, the brain regions involved in birdsong learning, perception, and production have been identified and characterized in detail. In particular, the caudal medial nidopallium (the avian analog of the mammalian auditory‐association cortex) has been found to contain the neural substrate of auditory memory, paving the way for analyses of the underlying molecular mechanisms. Recently, the zebra finch genome was sequenced, (...) and annotated cDNA databases representing over 15,000 unique brain‐expressed genes are available, enabling high‐throughput gene expression analyses. Here we review the involvement of immediate early genes (e.g. zenk and arc), their downstream targets (e.g. synapsins), and their regulatory signaling pathways (e.g. MAPK/ERK) in songbird memory. We propose that in‐depth investigations of zenk‐ and ERK‐dependent cascades will help to further unravel the molecular basis of auditory memory. (shrink)

The developing neuromuscular junction has provided an important paradigm for studying synapse formation. An outstanding feature of neuromuscular differentiation is the aggregation of acetylcholine receptors (AChRs) at high density in the postsynaptic membrane. While AChR aggregation is generally believed to be induced by the nerve, the mechanisms underlying aggregation remain to be clarified. A 43‐kD protein (43k) normally associated with the cytoplasmic aspect of AChR clusters has long been suspected of immobilizing AChRs by linking them to the cytoskeleton. In recent (...) studies, the AChR clustering activity of 43k has, at last, been demonstrated by expressing recombinant AChR and 43k in non‐muscle cells. Mutagenesis of 43k has revealed distinct domains within the primary structure which may be responsible for plasma membrane targeting and AChR binding. Other lines of study have provided clues as to how nerve‐derived (extracellular) AChR‐cluster inducing factors such as agrin might activate 43k‐driven postsynaptic membrane specialization. (shrink)

Recent experiments have begun to decipher the molecular dialog that mediates differentiation at sites of synaptic between neurons and their targets. It had been hypothesized that the protein agrin is released by axon terminals at embryonic neuromuscular junctions and binds to a receptor on the myofiber surface to trigger postsynaptic differentiation. Now a genetic ‘Knockout’ experiment has confirmed the essential role of agrin in signaling between developing nerve and muscle(1). A second ‘knockout’ has shown that the muscle‐specific receptor tyrosine kinase (...) MuSK is a critical element in the agrin‐induced signaling cascade(2). Additional results suggest that MuSK may comprise a portion of the agrin receptor(3). (shrink)

Neuromuscular synapses are highly dynamic structures that respond to both intercellular and intracellular cues to manipulate synaptic form. A variety of post‐translational modifications of synaptic proteins are used to regulate synaptic plasticity. A recent report by DiAntonio et al.(1) shows that two ubiquitin pathway proteins, Highwire and Fat facets, may be mutually antagonistic regulators of presynaptic growth at the Drosophila neuromuscular junction. This work adds support to the emerging idea that ubiquitin, a polypeptide that targets proteins for proteasomal degradation, (...) regulates synaptic development. BioEssays 24:13–16, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

During late embryonic and early postnatal development, synaptic connections are extensively modified so that some functional connections are weakened and eliminated from a neural circuit while others are strengthened and maintained. The mechanisms that underlie synapse elimination are beginning to be understood from studies of the neuromuscular junction. A recent paper(1) provides some intriguing insights into the role proteases may play in the developmental disassembly of neuromuscular synapses.

The ubiquitin proteasome system is a potent regulatory mechanism used to control protein stability in numerous cellular processes, including neural development. Many neurodegenerative diseases are featured by the accumulation of UPS‐associated proteins, suggesting the UPS dysfunction may be crucial for pathogenesis. Recent experiments have highlighted the UPS as a key player during synaptic development. Here we summarize recent discoveries centered on the role of the UPS in synapse remodeling and draw attention to the potential link between the synaptic UPS dysfunction (...) and the pathology of neurodegenerative diseases. BioEssays 30:1075–1083, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we propose a spiking neuronal network implementation that can be entrained to form a dynamical model of the temporal and causal relationships between events that it observes. The network uses spike-time (...) dependent plasticity, long-term depression, and heterosynaptic competition rules to implement Rescorla–Wagner-like learning. Transmission delays between neurons allow the network to learn a forward model of the temporal relationships between events. Within this framework, biologically realistic synaptic plasticity rules account for well-known behavioral data regarding cognitive causal assumptions such as backwards blocking and screening-off. These models can then be run as emulators for state inference. Furthermore, this mechanism is capable of copying synaptic connectivity patterns between neuronal networks by observing the spontaneous spike activity from the neuronal circuit that is to be copied, and it thereby provides a powerful method for transmission of circuit functionality between brain regions. (shrink)

SNAREs (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock‐and‐key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as the synaptic core (...) complex, is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non‐cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short‐term synaptic plasticity. BioEssays 24:926–936, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

CALHM1 was recently demonstrated to be a voltage‐gated ATP‐permeable ion channel and to serve as a bona fide conduit for ATP release from sweet‐, umami‐, and bitter‐sensing type II taste cells. Calhm1 is expressed in taste buds exclusively in type II cells and its product has structural and functional similarities with connexins and pannexins, two families of channel protein candidates for ATP release by type II cells. Calhm1 knockout in mice leads to loss of perception of sweet, umami, and bitter (...) compounds and to impaired gustatory nerve responses to these tastants. These new studies validate the concept of ATP as the primary neurotransmitter from type II cells to gustatory neurons. Furthermore, they identify voltage‐gated ATP release through CALHM1 as an essential molecular mechanism of ATP release in taste buds. We discuss these new findings, as well as unresolved issues in peripheral taste signaling that we hope will stimulate future research. (shrink)

Vadim Fedulov,1 Christopher S. Rex,2 Danielle A. Simmons,3 Linda Palmer,4 Christine M. Gall,1,2 and Gary Lynch.

Recently a number of complex electrophysiological responses to neurotransmitters have been observed that cannot be described as simple excitation or inhibition. These responses are often characterized as modulatory, although there is no consensus on what defines modulation. Morphological studies reveal certain neurotransmitters stored in what might be release sites without synaptic contact. There is no direct evidence for nonsynaptic release from CNS sites, although such release does occur in the periphery and in invertebrates. Nonsynaptic release might provide a basis for (...) diffuse one-cell-to-many communication, but it might also simply be a means of sending the transmitter to a broader area of a single neuron than occurs in typical synapses. Several kinds of macromolecules have been found to be transported in a retrograde direction – and in some cases transsynaptically. There have been suggestions that some neurons may release more than one type of transmitter. Particularly intriguing is the possibility of release of substances that modulate actions of a primary transmitter. Taken together this range of evidence suggests that neurons may use a variety of forms of molecular communication in addition to traditionally described synaptic transmission.Several authors have suggested modes of communication distinct from classical synaptic transmission and have classified released substances using terms such as neurohumor, neurohormone, neuroregulator, and modulator. These suggestions have the heuristic value of drawing together diverse kinds of data, but it remains to be established that the pieces fit together in that fashion – for example, that complex electrophysiological effects are associated with substances released nonsynaptically. In order to reduce confusion, a flexible, generic approach to nomenclature for substances released from neurons and for hypothetical modes of communication is recommended. Some behavioral implications of nonconventional transmission are considered. (shrink)

Capacity of conscious agents to perform genuine choices among future alternatives is a prerequisite for moral responsibility. Determinism that pervades classical physics, however, forbids free will, undermines the foundations of ethics, and precludes meaningful quantification of personal biases. To resolve that impasse, we utilize the characteristic indeterminism of quantum physics and derive a quantitative measure for the amount of free will manifested by the brain cortical network. The interaction between the central nervous system and the surrounding environment is shown to (...) perform a quantum measurement upon the neural constituents, which actualize a single measurement outcome selected from the resulting quantum probability distribution. Inherent biases in the quantum propensities for alternative physical outcomes provide varying amounts of free will, which can be quantified with the expected information gain from learning the actual course of action chosen by the nervous system. For example, neuronal electric spikes evoke deterministic synaptic vesicle release in the synapses of sensory or somatomotor pathways, with no free will manifested. In cortical synapses, however, vesicle release is triggered indeterministically with probability of 0.35 per spike. This grants the brain cortex, with its over 100 trillion synapses, an amount of free will exceeding 96 terabytes per second. Although reliable deterministic transmission of sensory or somatomotor information ensures robust adaptation of animals to their physical environment, unpredictability of behavioral responses initiated by decisions made by the brain cortex is evolutionary advantageous for avoiding predators. Thus, free will may have a survival value and could be optimized through natural selection. (shrink)

The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) of 30 sec) and (...) the durations of RP (>30 min) strongly suggests that some intracellular biochemical machinery is involved. Pharmacological evidence suggests that protein kinases are involved in RP of inhibitory synapses and LTD of excitatory PF synapses. Besides the well-described LTD, RP could be a cellular mechanism that plays an important role in motor learning. (shrink)

The discovery of participation of astrocytes as active elements in glutamatergic tripartite synapses (composed by functional units of two neurons and one astrocyte) has led to the construction of models of cognitive functioning in the human brain, focusing on associative learning, sensory integration, conscious processing and memory formation/retrieval. We have modelled human cognitive functions by means of an ensemble of functional units (tripartite synapses) connected by gap junctions that link distributed astrocytes, allowing the formation of intra- and intercellular (...) calcium waves that putatively mediate large-scale cognitive information processing. The model contains a diagram of molecular mechanisms present in tripartite synapses and contributes to explain the physiological bases of cognitive functions. It can be potentially expanded to explain emotional functions and psychiatric phenomena. (shrink)

Long-term potentiation (LTP) is operationally defined as a long-lasting increase in synaptic efficacy following high-frequency stimulation of afferent fibers. Since the first full description of the phenomenon in 1973, exploration of the mechanisms underlying LTP induction has been one of the most active areas of research in neuroscience. Of principal interest to those who study LTP, particularly in the mammalian hippocampus, is its presumed role in the establishment of stable memories, a role consistent with descriptions of memory formation. Other characteristics (...) of LTP, including its rapid induction, persistence, and correlation with natural brain rhythms, provide circumstantial support for this connection to memory storage. Nonetheless, there is little empirical evidence that directly links LTP to the storage of memories. In this target article we review a range of cellular and behavioral characteristics of LTP and evaluate whether they are consistent with the purported role of hippocampal LTP in memory formation. We suggest that much of the present focus on LTP reflects a preconception that LTP is a learning mechanism, although the empirical evidence often suggests that LTP is unsuitable for such a role. As an alternative to serving as a memory storage device, we propose that LTP may serve as a neural equivalent to an arousal or attention device in the brain. Accordingly, LTP may increase in a nonspecific way the effective salience of discrete external stimuli and may thereby facilitate the induction of memories at distant synapses. Other hypotheses regarding the functional utility of this intensely studied mechanism are conceivable; the intent of this target article is not to promote a single hypothesis but rather to stimulate discussion about the neural mechanisms underlying memory storage and to appraise whether LTP can be considered a viable candidate for such a mechanism. (shrink)

Les rituels sont les synapses dans le tissu culturel d'où sont issus les éléments qui gouvernent la vie en commun et la communication des êtres humains. Il en est ainsi depuis le commencement de toute société humaine. Mais ce n'est qu'au XX siècle que se manifeste un véritable intérêt pour le fonctionnement et l'importance culturelle des rituels. Il s'agit d'un tournant inspiré par les théories des ethnologues, et placé sous le signe du cultural turn et du performative turn du (...) XX siècle. On se détourne alors des pratiques jusque-là en vigueur de l'abstraction et de la représentation. Or, depuis le «Banquet» de Platon et l'instauration de la «Cène» chrétienne, l'un des rituels les plus importants est l'acte socialement codé de l'ingestion de nourriture, le repas. Avec l'Eat art dont il est le concepteur, Daniel Spoerri a repris ce thème et contribué, par le truchement du rituel piège, à poser un regard neuf sur l'acte de manger au XXe siècle. Tel que Spoerri le met en scène, le «rituel piège» attire l'attention sur le rôle de fondation de sens que joue le rituel dans la culture. Mais il fait apparaître également que les rituels se transforment en pièges idéologiques où tombe quiconque les prend « à la lettre » ou comme des évidences. Spoerri est un des artistes du XX et de ce début du XXI siècle qui, par le biais de leur art, rendent compte de la double fonction du rituel dans la culture: d'une part, le rituel maintient en vie le processus culturel; d'autre part, il est producteur d'idéologies qui font passer des mythes politiques pour naturels, prenant au piège consommateur de nourriture et consommateur d'art tout à la fois.Rituals are the synapses in the cultural fabric which has produced the elements that govern the coexistence and communication of human beings. This is so since the beginning of human society. But it is only 20th century that demonstrates a genuine interest in the operation and cultural importance of rituals. It is a milestone inspired by the theories of ethnologists, and placed under the sign of the cultural turn and performative turn of the twentieth century. It then turns practices far into force of abstraction and representation. However, since the "Banquet" of Plato and the establishment of the "Last Supper" Christian, one of the most important rituals is the act socially coded ingestion of food, meal. Eat with the art of which he is the designer, Daniel Spoerri took up this theme and contributed through the ritual trap, put a new perspective on the act of eating in the twentieth century. Spoerri as the stages, the "ritual trap" draws attention to the role of Foundation meaningful ritual plays in the culture. But it also shows that the rituals are transformed into ideological traps which falls whoever takes "the letter" or as evidence. Spoerri is one of the artists of the 20th and the beginning of the 21st century, through their art, reflect the dual role of ritual in culture: on the one hand, the ritual keeps life the cultural process, on the other hand, it is a producer of ideologies that pass for political myths natural trapping consumer food and consumer of art at the same time. (shrink)

A common misunderstanding of the selected effects theory of function is that natural selection operating over an evolutionary time scale is the only functionbestowing process in the natural world. This construal of the selected effects theory conflicts with the existence and ubiquity of neurobiological functions that are evolutionary novel, such as structures underlying reading ability. This conflict has suggested to some that, while the selected effects theory may be relevant to some areas of evolutionary biology, its relevance to neuroscience is (...) marginal. This line of reasoning, however, neglects the fact that synapses, entire neurons, and potentially groups of neurons can undergo a type of selection analogous to natural selection operating over an evolutionary time scale. In the following, I argue that neural selection should be construed, by the selected effect theorist, as a distinct type of function-bestowing process in addition to natural selection. After explicating a generalized selected effects theory of function and distinguishing it from similar attempts to extend the selected effects theory, I do four things. First, I show how it allows one to identify neural selection as a distinct function-bestowing process, in contrast to other forms of neural structure formation such as neural construction. Second, I defend the view from one major criticism, and in so doing I clarify the content of the view. Third, I examine drug addiction to show the potential relevance of neural selection to neuroscientific and psychological research. Finally, I endorse a modest pluralism of function concepts within biology. (shrink)

The posterior parietal cortex (PPC) is the most likely site where egocentric spatial relationships are represented in the brain. PPC cells receive visual, auditory, somaesthetic, and vestibular sensory inputs; oculomotor, head, limb, and body motor signals; and strong motivational projections from the limbic system. Their discharge increases not only when an animal moves towards a sensory target, but also when it directs its attention to it. PPC lesions have the opposite effect: sensory inattention and neglect. The PPC does not seem (...) to contain a “map” of the location of objects in space but a distributed neural network for transforming one set of sensory vectors into other sensory reference frames or into various motor coordinate systems. Which set of transformation rules is used probably depends on attention, which selectively enhances the synapses needed for making a particular sensory comparison or aiming a particular movement. (shrink)

This paper examines the interplay between conceptual structure and the evolution of scientific concepts, arguing that concepts are fundamentally ‘forward-looking’ constructs. Drawing on empirical studies of similarity and categorization, I explicate the way in which the conceptual taxonomy highlights the ‘relevant respects’ for similarity judgments involved in categorization. I then propose that this taxonomy provides some of the cognitive underpinnings of the ongoing development of scientific concepts. I use the concept synapse to illustrate my proposal, showing how conceptual taxonomy both (...) facilitates and constrains the accommodation of newly discovered phenomena. I end by briefly considering the implications of the proposed approach for a normative evaluation of scientific concepts. (shrink)

To comprehend pain, disease, death and suffering as being meaningful - beyond the firing of synapses, the collapse of human abilities, and the mere end of life - requires a context in which to evaluate essential connotations, as well as to place and integrate understandings. If pain and suffering are to have enduring significance, they must be situated within a nest of ontological background assumptions, standards of inquiry, and epistemological foundations. Where secular bioethics fails to give deep meaning to (...) suffering, Christian bioethics succeeds. This essay analyzes the divergent meanings of suffering endorsed by the various Christian religions as conceptualized through the different metaphysical, epistemological, and sociological assumptions of each religion. (shrink)

While much of the recent literature on mechanisms has emphasized the superiority of mechanisms and mechanistic explanation over laws and nomological explanation, paradigmatic mechanisms—e.g., clocks or synapses—actually exhibit a great deal of stability in their behavior. And while mechanisms of this kind are certainly of great importance, there are many events that do not occur as a consequence of the operation of stable mechanisms. Events of natural and human history are often the consequence of causal processes that are ephemeral (...) and capricious. In this paper I shall argue that, notwithstanding their ephemeral nature, these processes deserve to be called mechanisms. Ephemeral mechanisms share important characteristics with their more stable cousins, and these shared characteristics will help us to understand connections between scientific and historical explanation. (shrink)

Standard semantic information processing models—information in; information processed; information out —lend themselves to standard models of the functioning of the brain in terms, e.g., of threshold-switch neurons connected via classical synapses. That is, in terms of sophisticated descendants of McCulloch and Pitts models. I argue that both the cognition and the brain sides of this framework are incorrect: cognition and thought are not constituted as forms of semantic information processing, and the brain does not function in terms of passive (...) input processing units organized as neural nets. An alternative framework is developed that models cognition and thought not in terms of semantic information processing, and, correspondingly, models brain functional processes also not in terms of semantic information processing. As alternative to such models: I outline a pragmatist oriented, interaction based, model of representation; derive from this model a fundamental framework of constraints on how the brain must function; show that such a framework is in fact found in the brain, and develop the outlines of a broader model of how mental processes can be realized within this alternative framework. Part I of this discussion focuses on some criticisms of standard modeling frameworks for representation and cognition, and outlines an alternative interactivist, pragmatist oriented, model. In part II, the focus is on the fact that the brain does not, in fact, function in accordance with standard passive input processing models—e.g., information processing models. Instead, there are multiple endogenously active processes at multiple spatial and temporal scales across multiple kinds of cells. A micro-functional model that accounts for, and even predicts, these multi-scale phenomena in generating emergent representation and cognition is outlined. That is, I argue that the interactivist model of representation outlined offers constraints on how the brain should function that are in fact empirically found, and, in reverse, that the multifarious details of brain functioning entail the pragmatist representational model—a very strong interrelationship. In the sequel paper, starting with part III, this model is extended to address macro-functioning in the CNS. In part IV, I offer a discussion of an approach to brain functioning that has some similarities with, as well as differences from, the model presented here: sometimes called the predictive brain approach. (shrink)

During tumor evolution, cancer cells use the tumor‐stroma crosstalk to reorganize the microenvironment for maximum robustness of the tumor. The success of immune checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer treatment should not aim to influence the individual components of super complex intracellular interactomes (molecular targeting), but try to disrupt the intercellular interactions between cancer and stromal cells, thus breaking the tumor as a whole. Arguments are provided in favor of a hypothesis that such interactions include (...) formation of synapse‐like structures (interfaces) where the interacting cells are located at a distance of ∼10–15 nm. Within these interfaces, molecules initiating and strengthening the interaction are organized, and allow optimum cross‐signaling; a very confined intercellular space facilitates the concentration of secreted cytokines, enhancing the paracrine cross‐communication. These features of tumors form a druggable cancer hallmark the tumor‐stroma symbiotic crosstalk—which represents a new target for efficient cancer drug discovery. (shrink)

The idea at the core of the New Mechanical account of explanation can be summarized in the claim that explaining means showing ‘how things work’. This simple motto hints at three basic features of Mechanistic Explanation (ME): ME is an explanation-how, that implies the description of the processes underlying the phenomenon to be explained and of the entities that engage in such processes. These three elements trace a fundamental contrast with the view inherited from Hume and later from strict logical (...) empiricism (see Creath 2017), focused on epistemic and formal features of science and according to which issues concerning the kind of entities and processes that lie within a theory’s domain are extraneous to science and belong instead to ontology or metaphysics. Philosophers belonging to the new mechanical philosophy believe that the received view of scientific explanation (Hempel 2001), pivoting on the notion of law of nature, overshadows this insight. Since its origin in the 17th century, mechanical philosophy aimed to explain natural phenomena by reducing them to mechanisms. Traditional attempts to define the concept of mechanism involved the identification of a limited set of fundamental elements as, for instance, contact action, action at a distance, inertial motion (see e.g. Hesse 2005), and, more recently, transmission of a mark, or of a conserved quantity (see Frisch, this volume). The new mechanical philosophy rejects this austere characterization of mechanisms and mechanistic explanation and aim at providing a novel, philosophically rigorous explication of the concept of mechanism and of its role in scientific explanation and practice. ME has been adopted with profit in philosophy of special sciences (for instance in biomedical sciences, e.g. in the explanation of chemical transmission at synapses ((Machamer, Darden and Craver 2000), MDC henceforth); but also in social sciences, e.g. the three kinds of social mechanisms in Coleman’s analysis of Max Weber’s account of the role of the Protestant ethic in the growth of capitalism (Hedström and Swedberg 1998)), where exceptionless regularities are rarely ever found. In physics, it is generally possible to formulate explanations in law-based form, with the result that the plurality of explanatory forms might be overlooked. This should not come as a surprise, given that physics was the main inspiration for logical empiricists, and, in particular, Newtonian physics was a template for Hempel’s formulation of the covering law model. However, this situation is unfortunate, since, we will argue, knowing how things work is often part of the explanation of physical phenomena. In this chapter, we provide an introduction to the basic features of ME, with specific focus on its application to physics (section 1). The main part of the chapter is devoted to the defence of two theses: on the one hand, some domains of physics are not compatible with mechanistic reasoning and explanation (section 2); on the other hand, a comprehensive account of explanation in physics can’t dispense with ME (section 3). (shrink)

Organelles transported along microtubules are normally moved to precise locations within cells. For example, synaptic vesiceles are transported to the neruronal synapse, the Golgi apparatus is generally found in a perinuclear location, and the membranes of the endoplasmic reticulum are actively extended to the cell periphery. The correct positioning of these organelles depends on microtubules and microtubule motors. Melanophores provide an extreme example of organized organelle transport. These cells are specialized to transport pigment granules, which are coordinately moved towards or (...) away from the cell center, and result in the cell appearing alternately light or dark. Melanophores have proved to be an ideal system for studying the mechanisms by which the cell controls the direction of its organelle transport. Pigment granule dispersion (the movement away from the cell center) requires protein phosphorylation, while pigment aggregation (the movement towards the cell center) requires protein dephosphorylation. The target of this phosphorylation and dephosphorylation event is a protein that interacts with the microtubule motor protein, kinesin. Thus, the direction of organelle transport along microtubules may be regulated by controlling the activity of a microtubule motor. (shrink)

This new six-volume collection from Routledge and Edition Synapse brings together key documents from the Victorian feminist campaign to establish and improve girls’ and women’s education. The set is divided into two sections, both of which incorporate materials that argue for the improvement of girls’ and women’s education as well as arguments made against education for girls and women. The first section focuses on the debate surrounding the quality of women’s education and the question of access to higher education for (...) women. This section also brings together documents from the feminist campaign with writing from the established press on the question of women’s higher education, and writings from the Social Sciences Association where many education reformers aired their views. The second section concentrates on the strengths and successes of Victorian women as educators, and highlights some of the most influential women in the field of education during this era. Drawing widely on articles from the feminist and established press, government papers, newspapers, professional and association journals, as well as memoirs, addresses, pamphlets, and reviews, this essential collection gives researchers excellent and comprehensive access to nineteenth-century debates on improving girls’ and women’s education, and women’s work as educators. (shrink)